Kava Extract for Stress

Overseen By Megan Erickson

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: Kava, Acetaminophen, Steroids, others

Disqualifiers: Pregnancy, Alcohol use, Liver disease, others

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether Kava extract, a dietary supplement, can influence cortisol levels, which are linked to stress, in healthy surgical nurses. Participants will receive either Kava extract (containing kavalactones) or a placebo for 28 days to compare effects. Nurses working in surgical services at the Mayo Clinic in Rochester, MN, who can fully participate and are willing to use birth control if necessary, may be eligible to join.

As an unphased trial, this study provides participants the opportunity to contribute to understanding the potential stress-reducing benefits of Kava extract.

Will I have to stop taking my current medications?

The trial requires participants to stop using kava, acetaminophen, oral corticosteroids, and kratom before joining. If you use acetaminophen, you must switch to an NSAID (a different type of pain reliever) during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that kava, a popular supplement, presents some safety concerns. Rare but serious cases of liver injury have been linked to kava use, with reports of liver damage leading to severe outcomes. Due to these concerns, Europe and Canada removed kava from the market in the early 2000s. While kava is sometimes used to help with anxiety, awareness of these safety issues is important. Prospective trial participants should be informed of these potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for stress, which often include medications like SSRIs or benzodiazepines, the Kava extract is derived from kavalactones, a natural compound found in the kava plant. Researchers are excited about Kava because it offers a potentially safer and more natural alternative with fewer side effects than synthetic drugs. Additionally, kavalactones work by modulating GABA receptors in the brain, which can promote relaxation and reduce anxiety, possibly providing relief faster than some traditional medications. This unique action and its natural origin make Kava an intriguing option for those seeking alternatives to conventional stress treatments.

What evidence suggests that Kava extract might be an effective treatment for stress?

Research has shown that kava extract, particularly its active ingredients called kavalactones, can help reduce anxiety symptoms. In several studies, kava outperformed a placebo, with one study showing it reduced anxiety by a moderate amount. Another analysis found kava to be 1.5 times more effective than a placebo. Kava has also shown promise in easing nervous tension and restlessness. In this trial, participants in the Kava Group will receive kavalactones for 28 days, while those in the Placebo Group will receive a placebo. While this study focuses on stress by measuring cortisol levels, existing evidence supports kava's potential in managing stress-related symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Brent Bauer, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for surgical service nurses at Mayo Clinic in Rochester, MN who can fully participate and agree to use birth control during the study. It's not for those pregnant, nursing, or trying to conceive; with recent kava use; allergies to kava; heavy alcohol users; on certain medications like steroids or kratom; or with significant liver, kidney diseases, hormonal imbalances, cancer history (except specific cases), or unstable medical conditions.

Inclusion Criteria

Willing to use birth control for the duration of the study (if of childbearing potential)

I can fully participate in all parts of the study.

Surgical services nurses at Mayo Clinic in Rochester, MN

Exclusion Criteria

I am willing to use approved birth control if I have a menstrual cycle and have sex with men.

I have been diagnosed with Addison's or Cushing's Disease.

I have a known imbalance in my stress hormones or take medication that affects these levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Kavalactones or placebo for 28 days

4 weeks

Baseline and end of treatment visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Kavalactones
• Placebo

Trial Overview The study tests the effects of Kavalactones (found in Kava extract) versus a placebo on stress levels by measuring cortisol in healthy nurses. Participants will either receive the Kavalactones supplement or a placebo without knowing which one they are taking.

How Is the Trial Designed?

Group I: Kava Group Experimental Treatment 1 Intervention

Subjects will receive Kavalactones for 28 days

Group II: Placebo Group Placebo Group 1 Intervention

Subjects will receive placebo for 28 days

Kavalactones is already approved in United States, European Union for the following indications:

Approved in United States as Kava for:

• Anxiety
• Stress relief
• Muscle relaxation

Approved in European Union as Kava for:

• Anxiety
• Stress relief

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Kava extract demonstrated anxiolytic effects and reduced stereotyped behaviors induced by amphetamine in mice, suggesting its potential to alleviate psychotic symptoms.

The study found that Kava extract decreased the activity of monoamine oxidase (MAO) enzymes in specific brain regions, which may contribute to its therapeutic effects in managing anxiety and psychosis-like symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kava decreases the stereotyped behavior induced by amphetamine in mice. Krum, BN., Molz de Freitas, C., Chiapinotto Ceretta, AP., et al.[2021]

Piper methysticum extract (kava kava) and its principal component, dihydrokavain, were found to reduce distress vocalizations in chicks subjected to social separation stress, indicating potential anxiolytic effects.

The study involved eight-day-old chicks receiving various treatments, showing that both kava extract and dihydrokavain can alleviate anxiety-like behaviors, suggesting their therapeutic potential for anxiety management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anxiolytic effects of kava extract and kavalactones in the chick social separation-stress paradigm. Smith, KK., Dharmaratne, HR., Feltenstein, MW., et al.[2019]

A study on Wistar rats, which were given ethanolic kava extract for 3 to 6 months, showed no signs of chronic toxicity, including no adverse effects on body weight or liver health.

These findings support the traditional use of kava preparations in the South Pacific and suggest that concerns about liver toxicity may be unfounded.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ethanolic kava extract: Results of a study of chronic toxicity in rats. Sorrentino, L., Capasso, A., Schmidt, M.[2010]

Kava extracts are generally well tolerated and associated with rare, mild, and reversible adverse events when used as a short-term treatment for anxiety, based on a systematic review of clinical evidence.

However, serious adverse events, including liver damage and neurological complications, have been reported, indicating the need for further research to better understand the risks associated with kava use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the safety of kava extract in the treatment of anxiety. Stevinson, C., Huntley, A., Ernst, E.[2018]

The report highlights concerns about adverse events associated with concentrated standardized preparations of kava, prompting a global safety evaluation of the herb following reports from Germany and Switzerland.

It argues that many reported adverse events may not be directly linked to kava itself, suggesting that the safety issues arise more from concentrated extracts rather than traditional preparations, and proposes measures to ensure safe kava use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kava--the unfolding story: report on a work-in-progress. Denham, A., McIntyre, M., Whitehouse, J.[2019]

A validated analytical method was developed to simultaneously quantify six major kavalactones in kava extracts, ensuring accurate quality control of these products.

Using a multi-standard approach for kavalactones resulted in significantly different content measurements compared to using only kavain as a standard, highlighting the importance of comprehensive testing for effective quality assurance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous quantitation of kavalactones in kava dry extracts: comparison of multi-standards and single standard validation approaches. Ferreira, JV., Pierotte, IC., Pianetti, GA., et al.[2021]

The Kava Anxiety Depression Spectrum Study (KADSS) is the first clinical trial to assess the effectiveness of an aqueous extract of kava for treating anxiety and depression, involving 60 adult participants over a 3-week period.

If the study finds that kava is both effective and safe, it could lead to its re-introduction in Europe, the UK, and Canada, benefiting both individuals with anxiety disorders and the economies of Pacific Island nations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kava Anxiety Depression Spectrum Study (KADSS): a mixed methods RCT using an aqueous extract of Piper methysticum. Sarris, J., Kavanagh, DJ., Adams, J., et al.[2009]

The synthesized compound 6-(4-fluorophenyl)-4-methoxy-5,6-dihydropyran-2-one (2d) demonstrated strong and dose-dependent analgesic effects in various pain models, outperforming some standard reference drugs.

The analgesic action of compound 2d does not involve the opioid system and does not affect motor performance, suggesting a unique mechanism of action that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kavain analogues as potential analgesic agents. Kormann, EC., Amaral, Pde A., David, M., et al.[2020]

Kava-kava has been traditionally used for its calming effects and is now marketed for anxiety and stress relief, showing minimal negative effects on cognitive function and reaction time.

While kava-kava is generally well tolerated and non-addictive at therapeutic doses, there have been recent reports of liver toxicity in some patients, raising concerns about potential side effects, especially with high doses or prolonged use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kava-kava and anxiety: growing knowledge about the efficacy and safety. Bilia, AR., Gallon, S., Vincieri, FF.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/10653213/

Efficacy of kava extract for treating anxiety These data imply that kava extract is superior to placebo as a symptomatic treatment for anxiety. Therefore, kava extract is an herbal treatment option for ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1744388118301981

A systematic review and analysis of randomized clinical trials Kava Kava was shown to be more effective than placebo in 3 of the 7 trials. A final risk ratio of 1.50 (95% CI: 1.12, 2.01) from responder rates was calculated ...

3. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-015-0986-5

Kava for the treatment of generalised anxiety disorder (K-GAD) Further, kava significantly reduced participant anxiety by −4.2, representing a moderate effect size (Cohen's d = 0.63). For participants with ...

4. digitalcommons.pcom.edu digitalcommons.pcom.edu/pa_systematic_reviews/83/

"Is Kava (Piper Methysticum) Safe and Effective for Reducing ... Results from the Conner et al study indicate that Kava use is effective in reducing anxiety in individuals with low baseline anxiety, but there were no ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33207379/

Kava (Piper methysticum) Extract for the Treatment of ... The most effective results were seen for nervous tension and restlessness, with better effects in patients with acute versus chronic complaints.

6. cdph.ca.gov cdph.ca.gov/Programs/CEH/DFDCS/CDPH%20Document%20Library/FDB/FoodSafetyProgram/KavaFactSheet.pdf

Consumer Fact Sheet—Kava - CDPH FDA issued a consumer advisory about the potential risk of severe liver injury associated with the use of kava-containing dietary supplements, ...

7. webmd.com webmd.com/vitamins/ai/ingredientmono-872/kava

Kava - Uses, Side Effects, and More Cases of liver damage and even some deaths have been linked to kava use. Because of this, kava was taken off the market in Europe and Canada in the early 2000s.

8. nccih.nih.gov nccih.nih.gov/health/kava

Kava: Usefulness and Safety | NCCIH - NIH What Do We Know About Safety? · Various kava products have been linked to rare cases of liver injury, some of which have been serious or even fatal. · Kava can ...

9. fda.gov fda.gov/media/169556/download

Scientific Memorandum: Kava (8/11/2020) Although there is some scientific evidence for the use of kava to treat anxiety, safety concerns over hepatotoxicity has resulted in withdrawal ...

10. ema.europa.eu ema.europa.eu/en/documents/herbal-report/draft-assessment-report-piper-methysticum-g-forst-rhizoma_en.pdf

Assessment report on Piper methysticum G. Forst., rhizoma WHO monograph describes for kava the traditional medicinal use to induce relaxation, reduce weight and treat fungal infections and the use in ...